Incremented Amyloid-beta values predict mortality during long-term follow-up in patients with acute myocardial infarction, both STEMI and NSTEMI

Abstract

Abstract Funding Acknowledgements None. Background Both the amyloid-β (Aβ) isoforms, namely Aβ1-40 and Aβ1-42 are implicated in the pathogenesis of Alzheimer’s disease through different mechanisms. While Aβ42 easily forms oligomers in brain, Aβ1-40 is more abundant in circulation where it exerts a pro-inflammatory role. Recently, Aβ1-40 has raised interest in the cardiovascular field for its contribution to atherosclerosis, more specifically through plaque formation and destabilization. However, to date, the prognostic role of Aβ1-40 in patients with acute myocardial infarction (AMI) is limited to NSTEMI. Purpose Since there is a need for better risk stratification of AMI patients, we analyzed the impact of plasma Aβ1-40 on long-term mortality in a cohort of real-world patients with AMI, including STEMI and NSTEMI. Further, we sought to identify predictors for elevated Aβ1-40 levels. Methods Blood samples were obtained from patients hospitalized for AMI and Aβ1-40 levels were evaluated with Human Aβ40 ELISA Kit. The endpoint was all-cause mortality. Results Our population included 1119 consecutive patients, with a mean age of 67 years, 72% male, 2/3 of them had a first ischemic event and 68.4% had STEMI diagnosis. The median plasma Aβ1-40 concentration on admission was 86.9 [54.5-128.9] pg/ml and there was no difference in Aβ1-40 levels between NSTEMI and STEMI (93.6 [61.2-130.9] Vs. 85.3 [52.9-128.7] pg/ml, respectively, p=0.1). At logistic regression multivariate analysis, higher Aβ1-40 levels were predicted by older age, worse left ventricular systolic function, HbA1C > 39 mmol/mol and GFR<60ml/min/m 2 (Fig.1a). From the final multivariable model, a nomogram for prediction of high levels of Aβ1-40 was computed (Fig.1b). One hundred ninety-three patients (17.2%) died, during the median follow-up of 57 [30 - 80] months. Patients who died had significantly higher levels of Aβ1-40 compared to alive patients (113.1 [67.9 – 159.5] Vs. 83.9 [52.5 – 122.6] pg/ml, p<0.01). Higher plasma Aβ1-40 values were associated with increased mortality risk, in both STEMI and NSTEMI (p<0.01) (Fig.2a). Further, at Cox multivariate analysis including the whole population, Aβ1-40 levels were predictive of mortality (HR 1.03, p=0.02), together with older age, higher Il-1β, GFR<60ml/min/m 2 and worse left ventricular systolic function (Fig.2b). The predictive value of our final model was superior to GRACE score for up to 60 months (AUC 0.830 (0.793 – 0.868) Vs 0.797 (0.756 – 0.837), respectively, p=0.03, Fig.2c), after which they were comparable. Conclusions Elevated levels of Aβ1-40 values are independent predictors of long-term mortality in a real-world cohort including both STEMI and NSTEMI patients.